Platelets, which constitute one type of blood cell components with important significance for hemostasis and thrombogenesis in the body, are released into the blood by a process in which hematopoietic stem cells in the bone marrow differentiate to megakaryocyte precursor cells which in turn differentiate to megakaryoblasts, and these megakaryoblasts then undergo maturation.
Numerous factors are known to function in the course of platelet production, and it is thrombopoietin (TPO) which is believed to be the most physiologically important factor (Lok, S. et al., Cell, 77, 1117(1994)). Thrombopoietin functions by activating its receptor c-mpl to transmit a signal into the cell (de Sauvage, F. J. et al., Nature, 369, 533(1994)), and its recognition as a specific factor in the megakaryocyte/platelet system has led to expectations for its application as an agent for treatment of various forms of thrombocytopenia.
However, using a protein such as thrombopoietin for medical purposes requires complex steps of culturing, purification and the like during its production process, and even when recombinant DNA techniques are used, the cost is generally much higher than for common low molecular weight compounds. Moreover, administration of formulations containing such proteins to humans introduces the problem of their antigenicity.
It has developed that low molecular weight compounds which have thrombopoietic action similar to that of thrombopoietin and low antigenicity, and which can be obtained by simple and inexpensive production processes. For example, Cwirla et al. have reported a peptide composed of 14 amino acids which can substitute for the action of thrombopoietin (Cwirla, S. E. et al., Science, 276, 1696(1997)). Even such compounds, however, fail to solve the problems alluded to above and are still inadequate for practical use as drug agents.